In the 1970s the introduction of in vitro procedures allowed creation of the human embryo outside the body aimed at treating couples with tubal factor infertility. The early successes achieved with assisted reproductive technologies (ART), although modest, motivated the ambition to improve efficiency on one hand and to extend treatment to other infertility indications. It was this intense effort to address fertilization failure plaguing early assisted fertilization cycles that brought to the development of intracytoplasmic sperm injection (ICSI) in 1992. This in vitro procedure has allowed clinicians to pinpoint the initial steps involved in the interaction of the parental gametes.
The reliability of sperm injection practices in term of high and consistent fertilization rates has allowed the generous application worldwide of this gamete insemination method. ICSI is now carried out in at least 53 countries and has currently generated about 2 million babies. This popular utilization unfortunately has not been accompanied by an increased affordability nor by an improved access through health insurances. Moreover, the inconsistency of the outcome for the reported data from different countries would call for an improved standardization with enhanced quality control. However, ICSI although it was developed as a treatment for male infertility, it has become the preferred method of insemination being performed in large centers at a rate of over 70%. Therefore, the development of an automated system is desirable that perform ICSI would become the sole in vitro insemination method.
Cho et al have described a gravity-driven pumping system to sort sperm samples (Cho et al. 2003, Passively driven integrated microfluidic system for separation of motile sperm, Anal Chem. 75(7):1671-1675). The device, termed a microscale integrated sperm sorter (MISS), contains inlet/outlet ports, fluid reservoirs, gravity-driven power sources, and converging microchannels with laminar flow, all integrated components working together to facilitate sperm sorting. This device was designed so a converging stream of semen and media would flow in parallel, in a laminar fashion within a microchannel. The two parallel streams only mix by diffusion at the interface between streams, but motile sperm are able to swim across the contacting streamline and into the media for collection. Nonmotile sperm, cellular debris, and seminal plasma do not cross this barrier and are shuttled into a waste reservoir.
Suh et al have described initial efforts to create some microfluidic components, namely for sperm selection, oocyte handling, microinsemination (but not ICSI), and embryo manipulation and culture, as well as the need for and benefits of integrated systems (Suh et al. 2003, Rethinking gamete/embryo isolation and culture with microfluidics, Hum Reprod Update. 9(5):451-61; Suh et al. 2005, Microfluidic Applications for Andrology, J Androl. 26(6):664-70).
Smith et al have provided a review in 2011 that discusses sperm selection and speculates on microinsemination of mouse oocytes and embryo culture (Smith et al. 2011, Microfluidics for gametes, embryos, and embryonic stem cells, Semin Reprod Med. 29(1):5-14). Smith is cofounder of the medical device company, Incept BioSystems™, which is using its “System for Microfluidic Assisted Reproductive Technology (SMART)” to create microfluidic IVF systems. Its first product is a device for embryo culture.
Unisense FertiliTech A/S markets an automated embryo incubator that incorporates a fully stable incubation environment with integrated respiration and time-lapse image acquisition; the latter allows embryo assessment (Raty et al. 2004, Lab on a Chip, 4:186-190).
Lu et al have described a disposable chip placed on a microscope where sperm and oocytes are placed into 2 separate chambers; a spermatozoon is selected and robotized ICSI performed on all oocytes executed by a human operator (Lu et al. 2011, Robotic ICSI, IEEE Trans Biomed Eng, 58:2102-2108). Adamo and Jensen also demonstrated proof of concept for microinjection of a fluorescent dye into a single cell (Adamo and Jensen 2008, Lab on a Chip, 8:1258-1261).
The devices described in the prior art perform different aspects of in vitro insemination ranging from sperm and oocyte preparation to actual insemination followed by embryo culture. Although the aforementioned prior art describes efforts to generate components of a complete, automated system, no such system has been created.